The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors

被引:170
作者
Antinore, MJ
Birrer, MJ
Patel, D
Nader, L
McCance, DJ
机构
[1] UNIV ROCHESTER,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642
[2] NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD 20850
关键词
AP1; E7; human papillomavirus; Jun;
D O I
10.1002/j.1460-2075.1996.tb00546.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The E7 gene product of human papillomavirus type 16 (HPV16) binds to the retinoblastoma gene product (pRb) and dissociates pRb-E2F complexes. However, the observation that the ability of E7 to bind pRb is not required for the HPV16-induced immortalization of primary keratinocytes prompted a search for other cellular factors bound by E7. Using a glutathione-S-transferase (GST) fusion protein system, we show that E7 complexes with AP1 transcription factors including c-Jun, JunB, JunD and c-Fos. The ability of E7 to complex with c-Jun in vivo is demonstrated by co-immunoprecipitation and the yeast two-hybrid system. An analysis of E7 point mutants in the GST system indicates that the E7 zinc-finger motif, but not the pRb binding domain, is involved in these interactions. Using c-Jun deletion mutants, E7 binding maps between amino acids 224 and 286 of c-Jun. E7 trans-activates c-Jun-induced transcription from a Jun responsive promoter, and this activity correlates with the ability of E7 mutants to bind Jun proteins. Finally, a transcriptionally inactive c-Jun deletion, which can bind E7, interferes with the E7-induced transformation of rat embryo fibroblasts in cooperation with an activated ras, indicating that the Jun-E7 interaction is physiologically relevant and that Jun factors may be targeted in the E7 transformation pathway.
引用
收藏
页码:1950 / 1960
页数:11
相关论文
共 72 条
[1]  
ABATE C, 1990, CELL GROWTH DIFFER, V1, P455
[2]   REDOX REGULATION OF FOS AND JUN DNA-BINDING ACTIVITY INVITRO [J].
ABATE, C ;
PATEL, L ;
RAUSCHER, FJ ;
CURRAN, T .
SCIENCE, 1990, 249 (4973) :1157-1161
[3]   THE TRANSACTIVATING DOMAIN OF THE C-JUN PROTO-ONCOPROTEIN IS REQUIRED FOR COTRANSFORMATION OF RAT EMBRYO CELLS [J].
ALANI, R ;
BROWN, P ;
BINETRUY, B ;
DOSAKA, H ;
ROSENBERG, RK ;
ANGEL, P ;
KARIN, M ;
BIRRER, MJ .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (12) :6286-6295
[4]  
AUSUBEL FM, 1990, CURRENT PROTOCOLS MO
[5]   ADENOVIRUS E1A PROTEINS CAN DISSOCIATE HETEROMERIC COMPLEXES INVOLVING THE E2F TRANSCRIPTION FACTOR - A NOVEL MECHANISM FOR E1A TRANSACTIVATION [J].
BAGCHI, S ;
RAYCHAUDHURI, P ;
NEVINS, JR .
CELL, 1990, 62 (04) :659-669
[6]  
BANKS L, 1990, ONCOGENE, V5, P1383
[7]   THE REGION OF THE HPV E7 ONCOPROTEIN HOMOLOGOUS TO ADENOVIRUS E1A AND SV40 LARGE T-ANTIGEN CONTAINS SEPARATE DOMAINS FOR RB BINDING AND CASEIN KINASE-II PHOSPHORYLATION [J].
BARBOSA, MS ;
EDMONDS, C ;
FISHER, C ;
SCHILLER, JT ;
LOWY, DR ;
VOUSDEN, KH .
EMBO JOURNAL, 1990, 9 (01) :153-160
[8]   PAPILLOMAVIRUS POLYPEPTIDE-E6 AND POLYPEPTIDE-E7 ARE ZINC-BINDING PROTEINS [J].
BARBOSA, MS ;
LOWY, DR ;
SCHILLER, JT .
JOURNAL OF VIROLOGY, 1989, 63 (03) :1404-1407
[9]  
BARTEL P, 1993, BIOTECHNIQUES, V14, P920
[10]   THE E6-E7 REGION OF HUMAN PAPILLOMAVIRUS TYPE-18 IS SUFFICIENT FOR TRANSFORMATION OF NIH-3T3 AND RAT-1 CELLS [J].
BEDELL, MA ;
JONES, KH ;
LAIMINS, LA .
JOURNAL OF VIROLOGY, 1987, 61 (11) :3635-3640